NM_014654.4:c.907G>A

Variant names:

• chr1-30874552-C-T
• rs4949184
• NM_014654.4:c.907G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014654.4(SDC3):​c.907G>A​(p.Asp303Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,613,856 control chromosomes in the GnomAD database, including 33,040 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4274 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28766 hom.)
• Consequence: SDC3 NM_014654.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 28 publications found

Genes affected

SDC3 (HGNC:10660): (syndecan 3) The protein encoded by this gene belongs to the syndecan proteoglycan family. It may play a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism. Allelic variants of this gene have been associated with obesity. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004136145).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014654.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC3	NM_014654.4	MANE Select	c.907G>A	p.Asp303Asn	missense	Exon 4 of 5	NP_055469.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC3	ENST00000339394.7	TSL:1 MANE Select	c.907G>A	p.Asp303Asn	missense	Exon 4 of 5	ENSP00000344468.6
	SDC3	ENST00000336798.11	TSL:1	c.733G>A	p.Asp245Asn	missense	Exon 2 of 3	ENSP00000338346.7

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33799 AN: 151956 Hom.: 4267 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.185 AC: 46551 AN: 251266 AF XY: 0.192

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0490

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.193 AC: 281912 AN: 1461780 Hom.: 28766 Cov.: 35 AF XY: 0.196 AC XY: 142444 AN XY: 727200

African (AFR) AF: 0.340 AC: 11382 AN: 33480

American (AMR) AF: 0.122 AC: 5474 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3068 AN: 26130

East Asian (EAS) AF: 0.0396 AC: 1571 AN: 39700

South Asian (SAS) AF: 0.292 AC: 25222 AN: 86252

European-Finnish (FIN) AF: 0.183 AC: 9782 AN: 53414

Middle Eastern (MID) AF: 0.176 AC: 1014 AN: 5764

European-Non Finnish (NFE) AF: 0.191 AC: 212669 AN: 1111940

Other (OTH) AF: 0.194 AC: 11730 AN: 60384

GnomAD4 genome AF: 0.223 AC: 33841 AN: 152076 Hom.: 4274 Cov.: 32 AF XY: 0.222 AC XY: 16482 AN XY: 74342

African (AFR) AF: 0.330 AC: 13682 AN: 41426

American (AMR) AF: 0.170 AC: 2601 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3472

East Asian (EAS) AF: 0.0496 AC: 257 AN: 5184

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4814

European-Finnish (FIN) AF: 0.172 AC: 1818 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12846 AN: 67984

Other (OTH) AF: 0.207 AC: 435 AN: 2106

Alfa AF: 0.204 Hom.: 7119

Bravo AF: 0.222

TwinsUK AF: 0.177 AC: 656

ALSPAC AF: 0.189 AC: 729

ESP6500AA AF: 0.310 AC: 1367

ESP6500EA AF: 0.182 AC: 1565

ExAC AF: 0.194 AC: 23542

Asia WGS AF: 0.162 AC: 565 AN: 3478

EpiCase AF: 0.184

EpiControl AF: 0.177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.050
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.30	T
Polyphen		0.0080	B
Vest4		0.042
MPC		0.066
ClinPred		0.039	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.094
gMVP		0.33
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4949184; hg19: chr1-31347399; COSMIC: COSV59578628; COSMIC: COSV59578628;