rs764800898

Variant names:

• chr19-16067730-T-A
• NM_001145160.2:c.106T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-16067730-T-A
• chr19-16067730-T-C
• chr19-16067730-T-G

Variant summary

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

The NM_001145160.2(TPM4):​c.106T>A​(p.Cys36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict 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: 32)
• Consequence: TPM4 NM_001145160.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.765

Genes affected

TPM4 (HGNC:12013): (tropomyosin 4) This gene encodes a member of the tropomyosin family of actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosins are dimers of coiled-coil proteins that polymerize end-to-end along the major groove in most actin filaments. They provide stability to the filaments and regulate access of other actin-binding proteins. In muscle cells, they regulate muscle contraction by controlling the binding of myosin heads to the actin filament. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

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=0.13033226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPM4	NM_001145160.2	c.106T>A	p.Cys36Ser	missense_variant	Exon 1 of 9		NP_001138632.1
TPM4	NM_001367836.1	c.-167T>A		5_prime_UTR_variant	Exon 1 of 9		NP_001354765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPM4	ENST00000646974.2	c.106T>A	p.Cys36Ser	missense_variant	Exon 1 of 9			ENSP00000494125.1
TPM4	ENST00000589897.1	c.106T>A	p.Cys36Ser	missense_variant	Exon 2 of 3	4		ENSP00000466158.1
TPM4	ENST00000586499.6	n.31T>A		non_coding_transcript_exon_variant	Exon 1 of 9	4		ENSP00000468246.2
TPM4	ENST00000647464.2	c.-3T>A		upstream_gene_variant				ENSP00000496648.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.92
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T;.;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.49	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.78	.;N;.
REVEL	Benign	0.28
Sift	Benign	1.0	.;T;.
Sift4G	Benign	0.46	T;T;.
Polyphen		0.0020	.;B;B
Vest4		0.14
MutPred		0.31		Loss of methylation at K35 (P = 0.0158);Loss of methylation at K35 (P = 0.0158);Loss of methylation at K35 (P = 0.0158);
MVP		0.80
ClinPred		0.74	D
GERP RS		3.5
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-16178540;