NM_001164442.2:c.430G>T

Variant names:

• chr5-64717969-G-T
• rs774124604
• NM_001164442.2:c.430G>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.430G>T​(p.Asp144Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,368,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D144N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SHISAL2B NM_001164442.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37
• 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=0.13690892).

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.430G>T	p.Asp144Tyr	missense	Exon 3 of 3	NP_001157914.1	A6NKW6
	SREK1IP1	NM_173829.4	MANE Select	c.*6415C>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.430G>T	p.Asp144Tyr	missense	Exon 3 of 3	ENSP00000373726.5	A6NKW6
	SHISAL2B	ENST00000509189.5	TSL:2	n.*330G>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000426194.1	D6RH14
	SHISAL2B	ENST00000512767.5	TSL:2	n.607G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1368984 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 675204

African (AFR) AF: 0.00 AC: 0 AN: 30772

American (AMR) AF: 0.00 AC: 0 AN: 30158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24864

East Asian (EAS) AF: 0.0000285 AC: 1 AN: 35088

South Asian (SAS) AF: 0.00 AC: 0 AN: 74884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075350

Other (OTH) AF: 0.00 AC: 0 AN: 57266

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0047	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.92	T
PhyloP100		3.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.017	D
Vest4		0.35
MutPred		0.39		Loss of disorder (P = 0.0357)
MVP		0.17
MPC		0.50
ClinPred		0.94	D
GERP RS		3.8
Varity_R		0.11
gMVP		0.50
Mutation Taster		=80/20	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: rs774124604; hg19: chr5-64013796;