NM_022486.5:c.2228C>G

Variant names:

• chr9-112041882-G-C
• rs1827755518
• NM_022486.5:c.2228C>G

Variant summary

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

The NM_022486.5(SUSD1):​c.2228C>G​(p.Ser743Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUSD1 NM_022486.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.35
• 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]

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.2228C>G	p.Ser743Cys	missense	Exon 16 of 17	NP_071931.2
	SUSD1	NM_001282640.2		c.*19C>G		3_prime_UTR	Exon 17 of 18	NP_001269569.1	Q6UWL2-2
	SUSD1	NM_001282643.2		c.*19C>G		3_prime_UTR	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.2228C>G	p.Ser743Cys	missense	Exon 16 of 17	ENSP00000363388.4	Q6UWL2-1
	SUSD1	ENST00000374264.6	TSL:1	c.*19C>G		3_prime_UTR	Exon 17 of 18	ENSP00000363382.2	Q6UWL2-2
	SUSD1	ENST00000861057.1		c.2225C>G	p.Ser742Cys	missense	Exon 16 of 17	ENSP00000531116.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461552 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727066

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44704

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111842

Other (OTH) AF: 0.00 AC: 0 AN: 60378

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	0.11
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.96	D
Vest4		0.52
MutPred		0.40		Loss of disorder (P = 1e-04)
MVP		0.75
MPC		0.43
ClinPred		0.87	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.17
Mutation Taster		=100/0	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: rs1827755518; hg19: chr9-114804162;