16-19017227-T-C

Position:

• chr16-19017227-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024847.4(TMC7):​c.460+629T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 151,908 control chromosomes in the GnomAD database, including 62,510 homozygotes. 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: 𝑓 0.90 (62510 hom., cov: 31)
• Consequence: TMC7 NM_024847.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

Genes affected

TMC7 (HGNC:23000): (transmembrane channel like 7) Predicted to enable mechanosensitive ion channel activity. Predicted to be involved in ion transmembrane transport. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC7	NM_024847.4	c.460+629T>C		intron_variant		ENST00000304381.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC7	ENST00000304381.10	c.460+629T>C		intron_variant		1	NM_024847.4	P1
TMC7	ENST00000421369.3	c.130+629T>C		intron_variant		1
TMC7	ENST00000569532.5	c.460+629T>C		intron_variant		2
TMC7	ENST00000568469.5	n.501+629T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137115 AN: 151790 Hom.: 62471 Cov.: 31

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.905

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.903 AC: 137210 AN: 151908 Hom.: 62510 Cov.: 31 AF XY: 0.905 AC XY: 67240 AN XY: 74280

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.987

Gnomad4 NFE AF: 0.959

Gnomad4 OTH AF: 0.903

Alfa AF: 0.942 Hom.: 57123

Bravo AF: 0.894

Asia WGS AF: 0.913 AC: 3176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs4265793; hg19: chr16-19028549;