chr19-54415614-G-A

Position:

• chr19-54415614-G-A

Variant summary

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

The NM_020659.4(TTYH1):​c.62G>A​(p.Arg21His) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTYH1 NM_020659.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607

Genes affected

TTYH1 (HGNC:13476): (tweety family member 1) This gene encodes a member of the tweety family of proteins. Members of this family function as chloride anion channels. The encoded protein functions as a calcium(2+)-independent, volume-sensitive large conductance chloride(-) channel. Three transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jan 2011]

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=0.0682663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTYH1	NM_020659.4	c.62G>A	p.Arg21His	missense_variant	1/14	ENST00000376530.8
TTYH1	NM_001005367.3	c.62G>A	p.Arg21His	missense_variant	1/13
TTYH1	NM_001201461.2	c.62G>A	p.Arg21His	missense_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTYH1	ENST00000376530.8	c.62G>A	p.Arg21His	missense_variant	1/14	1	NM_020659.4	P3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1408378 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 697758

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: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.85	D;.;.;D;.
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.068	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	2.9	N;N;N;N;N
REVEL	Benign	0.074
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.64	T;T;T;T;T
Polyphen		0.0030, 0.92, 0.011	.;B;P;.;B
Vest4		0.18, 0.16, 0.21
MutPred		0.55		.;Loss of MoRF binding (P = 0.0568);Loss of MoRF binding (P = 0.0568);Loss of MoRF binding (P = 0.0568);Loss of MoRF binding (P = 0.0568);
MVP		0.27
MPC		0.45
ClinPred		0.32	T
GERP RS		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.098
gMVP		0.50

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: rs1309041083; hg19: chr19-54926788;