5-129760605-G-T

Variant names:

• chr5-129760605-G-T
• NM_001257308.2:c.393G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001257308.2(MINAR2):​c.393G>T​(p.Lys131Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MINAR2 NM_001257308.2 missense, splice_region
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.34

Genes affected

MINAR2 (HGNC:33914): (membrane integral NOTCH2 associated receptor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000251680 (HGNC:58253):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 5-129760605-G-T is Pathogenic according to our data. Variant chr5-129760605-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 2443702.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINAR2	NM_001257308.2	c.393G>T	p.Lys131Asn	missense_variant, splice_region_variant	Exon 2 of 3	ENST00000564719.2	NP_001244237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MINAR2	ENST00000564719.2	c.393G>T	p.Lys131Asn	missense_variant, splice_region_variant	Exon 2 of 3	5	NM_001257308.2	ENSP00000454268.1
ENSG00000251680	ENST00000503616.5	n.284+1902C>A		intron_variant	Intron 3 of 4	3
ENSG00000251680	ENST00000653455.1	n.256+1902C>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hearing loss, autosomal recessive 120 Pathogenic:1

Feb 08, 2023

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	34
DANN	Uncertain	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.34	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.6	N
Sift	Benign	0.051	T
Sift4G	Benign	0.080	T
Vest4		0.44
MVP		0.56
GERP RS		4.8
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.98
SpliceAI score (max)		0.86		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.86		Position offset: 0

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: chr5-129096298;