NM_001164442.2:c.380A>T

Variant names:

• chr5-64717919-A-T
• rs1477806364
• NM_001164442.2:c.380A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164442.2(SHISAL2B):​c.380A>T​(p.Asn127Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000044 in 1,364,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: SHISAL2B NM_001164442.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.658
• 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]

SREK1IP1 (HGNC:26716): (SREK1 interacting protein 1) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to be involved in RNA splicing and mRNA processing. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08002809).

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.380A>T	p.Asn127Ile	missense	Exon 3 of 3	NP_001157914.1	A6NKW6
	SREK1IP1	NM_173829.4	MANE Select	c.*6465T>A		downstream_gene	N/A	NP_776190.1	Q8N9Q2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISAL2B	ENST00000389074.6	TSL:2 MANE Select	c.380A>T	p.Asn127Ile	missense	Exon 3 of 3	ENSP00000373726.5	A6NKW6
	SHISAL2B	ENST00000506473.5	TSL:2	n.*263A>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000426145.1	D6RH14
	SHISAL2B	ENST00000509189.5	TSL:2	n.*280A>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000426194.1	D6RH14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000162 AC: 2 AN: 123402 AF XY: 0.0000151

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: 0.00

Gnomad OTH exome AF: 0.000267

GnomAD4 exome AF: 0.00000440 AC: 6 AN: 1364828 Hom.: 0 Cov.: 30 AF XY: 0.00000743 AC XY: 5 AN XY: 673160

African (AFR) AF: 0.00 AC: 0 AN: 30380

American (AMR) AF: 0.00 AC: 0 AN: 28680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24736

East Asian (EAS) AF: 0.00 AC: 0 AN: 34808

South Asian (SAS) AF: 0.0000540 AC: 4 AN: 74076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074526

Other (OTH) AF: 0.0000350 AC: 2 AN: 57064

GnomAD4 genome Cov.: 33

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	0.071
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.66
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.019
Sift	Benign	0.17	T
Sift4G	Uncertain	0.013	D
Vest4		0.21
MutPred		0.27		Gain of helix (P = 0.0199)
MVP		0.10
MPC		0.13
ClinPred		0.082	T
GERP RS		1.2
Varity_R		0.13
gMVP		0.29
Mutation Taster		=98/2	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: rs1477806364; hg19: chr5-64013746;