5-64690664-T-A

Variant names:

• chr5-64690664-T-A
• NM_001164442.2:c.41T>A

Variant summary

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

The NM_001164442.2(SHISAL2B):​c.41T>A​(p.Leu14His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SHISAL2B NM_001164442.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

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

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=0.23467094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISAL2B	NM_001164442.2	c.41T>A	p.Leu14His	missense_variant	Exon 1 of 3	ENST00000389074.6	NP_001157914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISAL2B	ENST00000389074.6	c.41T>A	p.Leu14His	missense_variant	Exon 1 of 3	2	NM_001164442.2	ENSP00000373726.5
SHISAL2B	ENST00000506473.5	n.41T>A		non_coding_transcript_exon_variant	Exon 1 of 4	2		ENSP00000426145.1
SHISAL2B	ENST00000509189.5	n.41T>A		non_coding_transcript_exon_variant	Exon 1 of 4	2		ENSP00000426194.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.41T>A (p.L14H) alteration is located in exon 1 (coding exon 1) of the FAM159B gene. This alteration results from a T to A substitution at nucleotide position 41, causing the leucine (L) at amino acid position 14 to be replaced by a histidine (H). 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	0.28
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.76	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.075
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.056	T
Vest4		0.45
MutPred		0.40		Gain of solvent accessibility (P = 0.0105);
MVP		0.32
MPC		0.58
ClinPred		0.78	D
GERP RS		5.0
Varity_R		0.18
gMVP		0.38

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: chr5-63986491;