5-64717919-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISAL2B	NM_001164442.2	c.380A>T	p.Asn127Ile	missense_variant	Exon 3 of 3	ENST00000389074.6	NP_001157914.1
SREK1IP1	NM_173829.4	c.*6465T>A		downstream_gene_variant		ENST00000513458.9	NP_776190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISAL2B	ENST00000389074.6	c.380A>T	p.Asn127Ile	missense_variant	Exon 3 of 3	2	NM_001164442.2	ENSP00000373726.5
SREK1IP1	ENST00000513458.9	c.*6465T>A		downstream_gene_variant		1	NM_173829.4	ENSP00000427401.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000162 AC: 2 AN: 123402 Hom.: 0 AF XY: 0.0000151 AC XY: 1 AN XY: 66244

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 SAS exome AF: 0.0000576

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000540

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000350

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.380A>T (p.N127I) alteration is located in exon 3 (coding exon 3) of the FAM159B gene. This alteration results from a A to T substitution at nucleotide position 380, causing the asparagine (N) at amino acid position 127 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1477806364; hg19: chr5-64013746;