5-129748274-C-T

Variant names:

• chr5-129748274-C-T
• rs1393093908
• NM_001257308.2:c.84C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001257308.2(MINAR2):​c.84C>T​(p.Ala28Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,946 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. Synonymous variant affecting the same amino acid position (i.e. A28A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MINAR2 NM_001257308.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 0 publications found

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]

MINAR2 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 120

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CHSY3-AS1 (HGNC:58253):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.322 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257308.2. 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
	MINAR2	NM_001257308.2	MANE Select	c.84C>T	p.Ala28Ala	synonymous	Exon 1 of 3	NP_001244237.1	P59773

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINAR2	ENST00000564719.2	TSL:5 MANE Select	c.84C>T	p.Ala28Ala	synonymous	Exon 1 of 3	ENSP00000454268.1	P59773
	CHSY3-AS1	ENST00000503616.5	TSL:3	n.285-13212G>A		intron	N/A
	CHSY3-AS1	ENST00000653455.2		n.313-13212G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000781 AC: 1 AN: 128032 AF XY: 0.0000143

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1382946 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 682386

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31566

American (AMR) AF: 0.00 AC: 0 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078544

Other (OTH) AF: 0.00 AC: 0 AN: 57872

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.1
DANN	Benign	0.84
PhyloP100		-0.32
PromoterAI		-0.020	Neutral

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: rs1393093908; hg19: chr5-129083967;