chr4-153558281-A-G

Variant names:

• chr4-153558281-A-G
• rs991952644
• NM_001131007.2:c.573A>G

Variant summary

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

The NM_001131007.2(TMEM131L):​c.573A>G​(p.Arg191Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,696 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: 6.9e-7 (0 hom.)
• Consequence: TMEM131L NM_001131007.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744
• Publications: 0 publications found

Genes affected

TMEM131L (HGNC:29146): (transmembrane 131 like) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of immature T cell proliferation in thymus. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.8).
• BP7: Synonymous conserved (PhyloP=0.744 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131007.2. 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
	TMEM131L	NM_001131007.2	MANE Select	c.573A>G	p.Arg191Arg	synonymous	Exon 7 of 35	NP_001124479.1	A2VDJ0-5
	TMEM131L	NM_015196.4		c.573A>G	p.Arg191Arg	synonymous	Exon 7 of 35	NP_056011.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM131L	ENST00000409959.8	TSL:5 MANE Select	c.573A>G	p.Arg191Arg	synonymous	Exon 7 of 35	ENSP00000386787.3	A2VDJ0-5
	TMEM131L	ENST00000240487.5	TSL:1	c.156A>G	p.Arg52Arg	synonymous	Exon 3 of 29	ENSP00000240487.5	H0Y2M0
	TMEM131L	ENST00000409663.7	TSL:5	c.573A>G	p.Arg191Arg	synonymous	Exon 7 of 35	ENSP00000386574.3	A2VDJ0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447696 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 719568

⚠️ 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: 33266

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25850

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.00 AC: 0 AN: 85234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1100820

Other (OTH) AF: 0.00 AC: 0 AN: 59718

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.8
DANN	Benign	0.69
PhyloP100		0.74

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: rs991952644; hg19: chr4-154479433;