chr4-103589736-G-A

Variant names:

• chr4-103589736-G-A
• rs76121575
• NM_001059.3:c.1344C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001059.3(TACR3):​c.1344C>T​(p.Ser448Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,613,912 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (57 hom.)
• Consequence: TACR3 NM_001059.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.442
• Publications: 2 publications found

Genes affected

TACR3 (HGNC:11528): (tachykinin receptor 3) This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neurokinin 3, also referred to as neurokinin B. [provided by RefSeq, Jul 2008]

TACR3-AS1 (HGNC:55593): (TACR3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 4-103589736-G-A is Benign according to our data. Variant chr4-103589736-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 516718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.442 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00216 (329/152246) while in subpopulation EAS AF = 0.053 (274/5166). AF 95% confidence interval is 0.0479. There are 6 homozygotes in GnomAd4. There are 176 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001059.3. 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
	TACR3	NM_001059.3	MANE Select	c.1344C>T	p.Ser448Ser	synonymous	Exon 5 of 5	NP_001050.1	P29371
	TACR3-AS1	NR_186501.1		n.190-1471G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	ENST00000304883.3	TSL:1 MANE Select	c.1344C>T	p.Ser448Ser	synonymous	Exon 5 of 5	ENSP00000303325.2	P29371
	TACR3-AS1	ENST00000502936.1	TSL:2	n.190-1471G>A		intron	N/A
	TACR3-AS1	ENST00000512401.5	TSL:2	n.292-1471G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 330 AN: 152128 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0533

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00443 AC: 1113 AN: 251156 AF XY: 0.00397

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.0560

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00150 AC: 2188 AN: 1461666 Hom.: 57 Cov.: 32 AF XY: 0.00145 AC XY: 1057 AN XY: 727126

African (AFR) AF: 0.000658 AC: 22 AN: 33460

American (AMR) AF: 0.000157 AC: 7 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 36 AN: 26128

East Asian (EAS) AF: 0.0470 AC: 1867 AN: 39686

South Asian (SAS) AF: 0.00130 AC: 112 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1111858

Other (OTH) AF: 0.00174 AC: 105 AN: 60382

GnomAD4 genome AF: 0.00216 AC: 329 AN: 152246 Hom.: 6 Cov.: 32 AF XY: 0.00236 AC XY: 176 AN XY: 74434

African (AFR) AF: 0.000746 AC: 31 AN: 41550

American (AMR) AF: 0.000196 AC: 3 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.0530 AC: 274 AN: 5166

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000323 Hom.: 0

Bravo AF: 0.00251

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Hypogonadotropic hypogonadism 11 with or without anosmia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs76121575; hg19: chr4-104510893; COSMIC: COSV59201991;