5-64717949-A-C

Variant names:

• chr5-64717949-A-C
• NM_001164442.2:c.410A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164442.2(SHISAL2B):​c.410A>C​(p.Glu137Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000146 in 1,371,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SHISAL2B NM_001164442.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

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=0.19440672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISAL2B	NM_001164442.2	c.410A>C	p.Glu137Ala	missense_variant	Exon 3 of 3	ENST00000389074.6	NP_001157914.1
SREK1IP1	NM_173829.4	c.*6435T>G		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.410A>C	p.Glu137Ala	missense_variant	Exon 3 of 3	2	NM_001164442.2	ENSP00000373726.5
SREK1IP1	ENST00000513458.9	c.*6435T>G		downstream_gene_variant		1	NM_173829.4	ENSP00000427401.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1371842 Hom.: 0 Cov.: 30 AF XY: 0.00000296 AC XY: 2 AN XY: 676768

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: 0.0000132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.410A>C (p.E137A) alteration is located in exon 3 (coding exon 3) of the FAM159B gene. This alteration results from a A to C substitution at nucleotide position 410, causing the glutamic acid (E) at amino acid position 137 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0035	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.13
Sift	Benign	0.066	T
Sift4G	Pathogenic	0.0	D
Vest4		0.39
MutPred		0.17		Loss of solvent accessibility (P = 0.002);
MVP		0.15
MPC		0.53
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.12
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-64013776;