7-97736303-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003182.3(TAC1):c.294T>C(p.His98=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000258 in 1,611,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: TAC1 NM_003182.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.02

Genes affected

TAC1 (HGNC:11517): (tachykinin precursor 1) This gene encodes four products of the tachykinin peptide hormone family, substance P and neurokinin A, as well as the related peptides, neuropeptide K and neuropeptide gamma. These hormones are thought to function as neurotransmitters which interact with nerve receptors and smooth muscle cells. They are known to induce behavioral responses and function as vasodilators and secretagogues. Substance P is an antimicrobial peptide with antibacterial and antifungal properties. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 7-97736303-T-C is Benign according to our data. Variant chr7-97736303-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 741561.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAC1	NM_003182.3	c.294T>C	p.His98=	synonymous_variant	6/7	ENST00000319273.10
TAC1	NM_013997.3	c.249T>C	p.His83=	synonymous_variant	5/6
TAC1	NM_013996.3	c.289+1454T>C		intron_variant
TAC1	NM_013998.3	c.244+1454T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAC1	ENST00000319273.10	c.294T>C	p.His98=	synonymous_variant	6/7	1	NM_003182.3
TAC1	ENST00000346867.4	c.249T>C	p.His83=	synonymous_variant	5/6	3		P1
TAC1	ENST00000350485.8	c.289+1454T>C		intron_variant		5
TAC1	ENST00000491437.1	n.368T>C		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000372 AC: 93 AN: 250226 Hom.: 0 AF XY: 0.000510 AC XY: 69 AN XY: 135374

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00567

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.000255 AC: 372 AN: 1459152 Hom.: 0 Cov.: 29 AF XY: 0.000288 AC XY: 209 AN XY: 725964

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00622

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000946

Gnomad4 OTH exome AF: 0.000896

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74288

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.000576 Hom.: 0

Bravo AF: 0.000332

EpiCase AF: 0.000546

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	11
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142031557; hg19: chr7-97365615;