rs139120093

Variant names:

• chr12-50086319-G-T
• rs139120093
• NM_003076.5:c.336G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-50086319-G-T
• chr12-50086319-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003076.5(SMARCD1):​c.336G>T​(p.Gln112His) variant causes a missense change. The variant allele was found at a frequency of 0.00352 in 1,560,100 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0036 (7 hom.)
• Consequence: SMARCD1 NM_003076.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.20
• Publications: 9 publications found

Genes affected

SMARCD1 (HGNC:11106): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SMARCD1 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome 11

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• Coffin-Siris syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010879189).
• BP6: Variant 12-50086319-G-T is Benign according to our data. Variant chr12-50086319-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2642976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00247 (372/150528) while in subpopulation NFE AF = 0.00447 (302/67502). AF 95% confidence interval is 0.00406. There are 0 homozygotes in GnomAd4. There are 171 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 372 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD1	NM_003076.5	MANE Select	c.336G>T	p.Gln112His	missense	Exon 2 of 13	NP_003067.3
	SMARCD1	NM_139071.3		c.336G>T	p.Gln112His	missense	Exon 2 of 12	NP_620710.2	Q96GM5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD1	ENST00000394963.9	TSL:1 MANE Select	c.336G>T	p.Gln112His	missense	Exon 2 of 13	ENSP00000378414.4	Q96GM5-1
	SMARCD1	ENST00000381513.8	TSL:1	c.336G>T	p.Gln112His	missense	Exon 2 of 12	ENSP00000370924.4	Q96GM5-2
	SMARCD1	ENST00000547247.5	TSL:1	n.364G>T		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 372 AN: 150412 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000607

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000428

Gnomad FIN AF: 0.00158

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00447

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.00279 AC: 672 AN: 241002 AF XY: 0.00276

Gnomad AFR exome AF: 0.000935

Gnomad AMR exome AF: 0.000527

Gnomad ASJ exome AF: 0.00252

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00133

Gnomad NFE exome AF: 0.00502

Gnomad OTH exome AF: 0.00224

GnomAD4 exome AF: 0.00363 AC: 5114 AN: 1409572 Hom.: 7 Cov.: 33 AF XY: 0.00356 AC XY: 2498 AN XY: 701032

African (AFR) AF: 0.000782 AC: 25 AN: 31970

American (AMR) AF: 0.000650 AC: 27 AN: 41512

Ashkenazi Jewish (ASJ) AF: 0.00283 AC: 68 AN: 24008

East Asian (EAS) AF: 0.00 AC: 0 AN: 35590

South Asian (SAS) AF: 0.00102 AC: 87 AN: 85050

European-Finnish (FIN) AF: 0.00143 AC: 65 AN: 45448

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5502

European-Non Finnish (NFE) AF: 0.00434 AC: 4701 AN: 1083306

Other (OTH) AF: 0.00245 AC: 140 AN: 57186

GnomAD4 genome AF: 0.00247 AC: 372 AN: 150528 Hom.: 0 Cov.: 31 AF XY: 0.00232 AC XY: 171 AN XY: 73616

African (AFR) AF: 0.000605 AC: 25 AN: 41298

American (AMR) AF: 0.00112 AC: 17 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00233 AC: 8 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 5000

South Asian (SAS) AF: 0.000428 AC: 2 AN: 4678

European-Finnish (FIN) AF: 0.00158 AC: 16 AN: 10108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00447 AC: 302 AN: 67502

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00365 Hom.: 3

Bravo AF: 0.00233

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00287 AC: 349

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Coffin-Siris syndrome 11 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.011	T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.47
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.028	D
Polyphen		0.010	B
Vest4		0.60
MutPred		0.35		Gain of helix (P = 0.0143)
MVP		0.72
MPC		1.0
ClinPred		0.040	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.15
gMVP		0.79
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs139120093; hg19: chr12-50480102; COSMIC: COSV106083200; COSMIC: COSV106083200;