19-9214615-A-T

Position:

• chr19-9214615-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005191.3(OR7D4):​c.223T>A​(p.Ser75Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S75C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: OR7D4 NM_001005191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.311

Genes affected

OR7D4 (HGNC:8380): (olfactory receptor family 7 subfamily D member 4) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR7E24 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05285278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7D4	NM_001005191.3	c.223T>A	p.Ser75Thr	missense_variant	2/2	ENST00000641669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7D4	ENST00000641669.1	c.223T>A	p.Ser75Thr	missense_variant	2/2		NM_001005191.3	P1
OR7D4	ENST00000308682.3	c.223T>A	p.Ser75Thr	missense_variant	1/1			P1
OR7D4	ENST00000641244.1	c.223T>A	p.Ser75Thr	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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 16, 2023

The c.223T>A (p.S75T) alteration is located in exon 1 (coding exon 1) of the OR7D4 gene. This alteration results from a T to A substitution at nucleotide position 223, causing the serine (S) at amino acid position 75 to be replaced by a threonine (T). 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	0.081
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.9
DANN	Benign	0.82
DEOGEN2	Benign	0.0047	T;T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.63	.;.;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.48	N;N;N
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.2	.;.;N
REVEL	Benign	0.014
Sift	Benign	0.24	.;.;T
Sift4G	Benign	0.31	.;.;T
Polyphen		0.015	B;B;B
Vest4		0.072
MutPred		0.29		Gain of glycosylation at T76 (P = 0.1465);Gain of glycosylation at T76 (P = 0.1465);Gain of glycosylation at T76 (P = 0.1465);
MVP		0.28
MPC		0.074
ClinPred		0.18	T
GERP RS		-0.036
Varity_R		0.078
gMVP		0.042

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: chr19-9325291;