4-153558286-C-T

Variant summary

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

The NM_001131007.2(TMEM131L):c.578C>T(p.Ser193Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM131L NM_001131007.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52

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

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=0.14214912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM131L	NM_001131007.2	c.578C>T	p.Ser193Phe	missense_variant	7/35	ENST00000409959.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM131L	ENST00000409959.8	c.578C>T	p.Ser193Phe	missense_variant	7/35	5	NM_001131007.2	A2
TMEM131L	ENST00000240487.5	c.161C>T	p.Ser54Phe	missense_variant	3/29	1
TMEM131L	ENST00000409663.7	c.578C>T	p.Ser193Phe	missense_variant	7/35	5		P4
TMEM131L	ENST00000462540.1	n.321C>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454978 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 723900

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.578C>T (p.S193F) alteration is located in exon 7 (coding exon 7) of the KIAA0922 gene. This alteration results from a C to T substitution at nucleotide position 578, causing the serine (S) at amino acid position 193 to be replaced by a phenylalanine (F). 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	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.087	T;.;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.062
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	D;D;N
REVEL	Benign	0.16
Sift	Benign	0.042	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.98	D;D;.
Vest4		0.28
MutPred		0.39		Loss of disorder (P = 0.0098);Loss of disorder (P = 0.0098);.;
MVP		0.043
MPC		0.42
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.094
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1481090537; hg19: chr4-154479438;