chr9-112041931-C-T

Variant names:

• chr9-112041931-C-T
• rs780435594
• NM_022486.5:c.2179G>A

Variant summary

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

The NM_022486.5(SUSD1):​c.2179G>A​(p.Gly727Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: SUSD1 NM_022486.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44
• Publications: 2 publications found

Genes affected

SUSD1 (HGNC:25413): (sushi domain containing 1) Predicted to enable calcium ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299696 (HGNC:):

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_022486.5. 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
	SUSD1	NM_022486.5	MANE Select	c.2179G>A	p.Gly727Ser	missense	Exon 16 of 17	NP_071931.2
	SUSD1	NM_001282640.2		c.2244G>A	p.Arg748Arg	synonymous	Exon 17 of 18	NP_001269569.1	Q6UWL2-2
	SUSD1	NM_001282643.2		c.2139G>A	p.Arg713Arg	synonymous	Exon 15 of 16	NP_001269572.1	F8WAQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUSD1	ENST00000374270.8	TSL:1 MANE Select	c.2179G>A	p.Gly727Ser	missense	Exon 16 of 17	ENSP00000363388.4	Q6UWL2-1
	SUSD1	ENST00000374264.6	TSL:1	c.2244G>A	p.Arg748Arg	synonymous	Exon 17 of 18	ENSP00000363382.2	Q6UWL2-2
	SUSD1	ENST00000861057.1		c.2176G>A	p.Gly726Ser	missense	Exon 16 of 17	ENSP00000531116.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000519 AC: 13 AN: 250458 AF XY: 0.0000443

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000452 AC: 66 AN: 1461738 Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26 AN XY: 727178

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

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: 0.0000576 AC: 64 AN: 1111938

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.4
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.34
Sift	Benign	0.48	T
Sift4G	Uncertain	0.049	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.24		Loss of helix (P = 0.0237)
MVP		0.79
MPC		0.21
ClinPred		0.30	T
GERP RS		5.1
Varity_R		0.15
Mutation Taster		=99/1	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: rs780435594; hg19: chr9-114804211;