2-216415439-C-T

Variant names:

• chr2-216415439-C-T
• rs149510554
• NM_014140.4:c.735C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_014140.4(SMARCAL1):​c.735C>T​(p.Gly245Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G245G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: SMARCAL1 NM_014140.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts U:1 B:2
• Conservation: PhyloP100: 1.04
• Publications: 1 publications found

Genes affected

SMARCAL1 (HGNC:11102): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. [provided by RefSeq, Jul 2008]

SMARCAL1 Gene-Disease associations (from GenCC):

• Schimke immuno-osseous dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 2-216415439-C-T is Benign according to our data. Variant chr2-216415439-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 532003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014140.4. 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
	SMARCAL1	NM_014140.4	MANE Select	c.735C>T	p.Gly245Gly	synonymous	Exon 3 of 18	NP_054859.2
	SMARCAL1	NM_001127207.2		c.735C>T	p.Gly245Gly	synonymous	Exon 3 of 18	NP_001120679.1	Q9NZC9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAL1	ENST00000357276.9	TSL:2 MANE Select	c.735C>T	p.Gly245Gly	synonymous	Exon 3 of 18	ENSP00000349823.4	Q9NZC9
	SMARCAL1	ENST00000358207.9	TSL:1	c.735C>T	p.Gly245Gly	synonymous	Exon 3 of 18	ENSP00000350940.5	Q9NZC9
	SMARCAL1	ENST00000392128.6	TSL:1	c.327C>T	p.Gly109Gly	synonymous	Exon 1 of 15	ENSP00000375974.2	H7BYI2

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152096 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000521 AC: 13 AN: 249522 AF XY: 0.0000370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000805

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000793 AC: 116 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.0000688 AC XY: 50 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000935 AC: 104 AN: 1112010

Other (OTH) AF: 0.000116 AC: 7 AN: 60394

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74388

African (AFR) AF: 0.0000481 AC: 2 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000966 Hom.: 0

Bravo AF: 0.0000869

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	1	Schimke immuno-osseous dysplasia (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	7.3
DANN	Benign	0.83
PhyloP100		1.0
PromoterAI		-0.020	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs149510554; hg19: chr2-217280162;