chr9-112052407-T-G

Variant names:

• chr9-112052407-T-G
• rs990595595
• NM_022486.5:c.2141A>C

Variant summary

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

The NM_022486.5(SUSD1):​c.2141A>C​(p.Gln714Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SUSD1 NM_022486.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00
• Publications: 0 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]

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.2141A>C	p.Gln714Pro	missense	Exon 15 of 17	NP_071931.2
	SUSD1	NM_001282640.2		c.2141A>C	p.Gln714Pro	missense	Exon 15 of 18	NP_001269569.1	Q6UWL2-2
	SUSD1	NM_001282643.2		c.2109+6021A>C		intron	N/A	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.2141A>C	p.Gln714Pro	missense	Exon 15 of 17	ENSP00000363388.4	Q6UWL2-1
	SUSD1	ENST00000374264.6	TSL:1	c.2141A>C	p.Gln714Pro	missense	Exon 15 of 18	ENSP00000363382.2	Q6UWL2-2
	SUSD1	ENST00000861057.1		c.2138A>C	p.Gln713Pro	missense	Exon 15 of 17	ENSP00000531116.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461754 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727178

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

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: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.0
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.19
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.93	P
Vest4		0.68
MutPred		0.38		Loss of stability (P = 0.0377)
MVP		0.64
MPC		0.43
ClinPred		0.96	D
GERP RS		3.2
Varity_R		0.24
gMVP		0.91
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs990595595; hg19: chr9-114814687; COSMIC: COSV100813141;