7-143444146-T-G

Variant names:

• chr7-143444146-T-G
• rs550023940
• NM_177437.1:c.694T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_177437.1(TAS2R60):​c.694T>G​(p.Ser232Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,614,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000078 (0 hom.)
• Consequence: TAS2R60 NM_177437.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.354
• Publications: 1 publications found

Genes affected

TAS2R60 (HGNC:20639): (taste 2 receptor member 60) This gene encodes a member of the bitter taste receptor family which belong to the G protein-coupled receptor superfamily and are predominantly expressed in taste receptor cells of the tongue and palate epithelia. This intronless taste receptor gene encodes a seven-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered together with eight other taste receptor genes on chromosome 7. [provided by RefSeq, Jul 2017]

EPHA1-AS1 (HGNC:27799): (EPHA1 antisense RNA 1)

ENSG00000309456 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05906892).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177437.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R60	NM_177437.1	MANE Select	c.694T>G	p.Ser232Ala	missense	Exon 1 of 1	NP_803186.1	P59551
	EPHA1-AS1	NR_033897.1		n.206+28947T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R60	ENST00000332690.1	TSL:6 MANE Select	c.694T>G	p.Ser232Ala	missense	Exon 1 of 1	ENSP00000327724.1	P59551
	EPHA1-AS1	ENST00000429289.5	TSL:1	n.206+28947T>G		intron	N/A
	EPHA1-AS1	ENST00000690912.2		n.227+28947T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 37 AN: 251116 AF XY: 0.000199

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.0000780 AC: 114 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 79 AN XY: 727244

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00110 AC: 95 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112008

Other (OTH) AF: 0.000116 AC: 7 AN: 60396

GnomAD4 genome AF: 0.0000459 AC: 7 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6 AN XY: 74502

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.000327 AC: 5 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.000140 AC: 17

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.041	N
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.35
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.055
Sift	Benign	0.25	T
Sift4G	Benign	0.28	T
Polyphen		0.95	P
Vest4		0.060
MutPred		0.41		Loss of glycosylation at S232 (P = 0.0173)
MVP		0.52
MPC		0.64
ClinPred		0.14	T
GERP RS		1.8
Varity_R		0.053
gMVP		0.027
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs550023940; hg19: chr7-143141239;