7-73865354-T-C

Position:

• chr7-73865354-T-C

Variant summary

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

The ENST00000320531.3(TMEM270):​c.434T>C​(p.Leu145Ser) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L145L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM270 ENST00000320531.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

Genes affected

TMEM270 (HGNC:23018): (transmembrane protein 270) Predicted to be integral component of 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=0.24922359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM270	NM_182504.4	c.434T>C	p.Leu145Ser	missense_variant	2/3	ENST00000320531.3	NP_872310.2
TMEM270	XM_011515785.3	c.143T>C	p.Leu48Ser	missense_variant	2/3		XP_011514087.1
TMEM270	XM_017011741.2	c.143T>C	p.Leu48Ser	missense_variant	2/3		XP_016867230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM270	ENST00000320531.3	c.434T>C	p.Leu145Ser	missense_variant	2/3	1	NM_182504.4	ENSP00000316775.2
TMEM270	ENST00000426490.1	n.*374T>C		non_coding_transcript_exon_variant	3/4	5		ENSP00000403621.1
TMEM270	ENST00000426490.1	n.*374T>C		3_prime_UTR_variant	3/4	5		ENSP00000403621.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 61

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

Dec 18, 2023

The c.434T>C (p.L145S) alteration is located in exon 2 (coding exon 2) of the WBSCR28 gene. This alteration results from a T to C substitution at nucleotide position 434, causing the leucine (L) at amino acid position 145 to be replaced by a serine (S). 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	0.25
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.0
DANN	Benign	0.93
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.14
Sift	Benign	0.081	T
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.36
MutPred		0.35		Loss of stability (P = 0.0213);
MVP		0.14
MPC		0.023
ClinPred		0.87	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.11

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: chr7-73279684;