NM_001164442.2:c.209G>C

Variant names:

• chr5-64695524-G-C
• rs1456561898
• NM_001164442.2:c.209G>C

Variant summary

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

The NM_001164442.2(SHISAL2B):​c.209G>C​(p.Gly70Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,382,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SHISAL2B NM_001164442.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63
• Publications: 0 publications found

Genes affected

SHISAL2B (HGNC:34236): (shisa like 2B) 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_001164442.2. 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
	SHISAL2B	NM_001164442.2	MANE Select	c.209G>C	p.Gly70Ala	missense	Exon 2 of 3	NP_001157914.1	A6NKW6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISAL2B	ENST00000389074.6	TSL:2 MANE Select	c.209G>C	p.Gly70Ala	missense	Exon 2 of 3	ENSP00000373726.5	A6NKW6
	SHISAL2B	ENST00000506473.5	TSL:2	n.*92G>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000426145.1	D6RH14
	SHISAL2B	ENST00000509189.5	TSL:2	n.*109G>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000426194.1	D6RH14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000699 AC: 1 AN: 143002 AF XY: 0.0000131

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000415

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000289 AC: 4 AN: 1382434 Hom.: 0 Cov.: 30 AF XY: 0.00000440 AC XY: 3 AN XY: 682158

African (AFR) AF: 0.00 AC: 0 AN: 31496

American (AMR) AF: 0.0000567 AC: 2 AN: 35302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25084

East Asian (EAS) AF: 0.00 AC: 0 AN: 35654

South Asian (SAS) AF: 0.00 AC: 0 AN: 78734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1077750

Other (OTH) AF: 0.00 AC: 0 AN: 57774

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.27
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.62	T
PhyloP100		7.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.78
MutPred		0.36		Loss of catalytic residue at L71 (P = 0.1742)
MVP		0.33
MPC		0.53
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.89
gMVP		0.60
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1456561898; hg19: chr5-63991351;