12-50086319-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003076.5(SMARCD1):​c.336G>C​(p.Gln112His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SMARCD1 NM_003076.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>C	p.Gln112His	missense	Exon 2 of 13	NP_003067.3
	SMARCD1	NM_139071.3		c.336G>C	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>C	p.Gln112His	missense	Exon 2 of 13	ENSP00000378414.4	Q96GM5-1
	SMARCD1	ENST00000381513.8	TSL:1	c.336G>C	p.Gln112His	missense	Exon 2 of 12	ENSP00000370924.4	Q96GM5-2
	SMARCD1	ENST00000547247.5	TSL:1	n.364G>C		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	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	Uncertain	0.090	D
MetaRNN	Uncertain	0.55	D
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	0.46
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		0.82	D
GERP RS		4.2
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;