Genetic Variant NM_022486.5:c.1915G>T (chr9-112058622-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022486.5(SUSD1):c.1915G>T(p.Ala639Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SUSD1
NM_022486.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.119

Publications

1 publications found

Variant links:

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]

SUSD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053625643).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUSD1	NM_022486.5	MANE Select	c.1915G>T	p.Ala639Ser	missense	Exon 14 of 17	NP_071931.2
SUSD1	NM_001282640.2		c.1915G>T	p.Ala639Ser	missense	Exon 14 of 18	NP_001269569.1	Q6UWL2-2
SUSD1	NM_001282643.2		c.1915G>T	p.Ala639Ser	missense	Exon 14 of 16	NP_001269572.1	F8WAQ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUSD1	ENST00000374270.8	TSL:1 MANE Select	c.1915G>T	p.Ala639Ser	missense	Exon 14 of 17	ENSP00000363388.4	Q6UWL2-1
SUSD1	ENST00000374264.6	TSL:1	c.1915G>T	p.Ala639Ser	missense	Exon 14 of 18	ENSP00000363382.2	Q6UWL2-2
SUSD1	ENST00000861057.1		c.1912G>T	p.Ala638Ser	missense	Exon 14 of 17	ENSP00000531116.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251118

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111990

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.9

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.018

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.78

M_CAP

Benign

0.017

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

-0.12

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.93

REVEL

Benign

0.031

Sift

Benign

0.33

Sift4G

Benign

0.10

Polyphen

0.34

Vest4

0.17

MutPred

0.23

Gain of phosphorylation at A639 (P = 0.0223)

MVP

0.12

MPC

0.27

ClinPred

0.060

GERP RS

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.39

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over