chr7-100881764-C-T

Variant names:

• chr7-100881764-C-T
• rs144415744
• NM_015908.6:c.357C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_015908.6(SRRT):​c.357C>T​(p.Asp119Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,613,596 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (13 hom.)
• Consequence: SRRT NM_015908.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53
• Publications: 7 publications found

Genes affected

SRRT (HGNC:24101): (serrate, RNA effector molecule) Enables mRNA cap binding complex binding activity and protein-macromolecule adaptor activity. Involved in primary miRNA processing. Located in nucleoplasm. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-100881764-C-T is Benign according to our data. Variant chr7-100881764-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657775.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.53 with no splicing effect.
• BS2: High AC in GnomAd4 at 366 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015908.6. 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
	SRRT	NM_015908.6	MANE Select	c.357C>T	p.Asp119Asp	synonymous	Exon 4 of 20	NP_056992.4
	SRRT	NM_001128852.2		c.357C>T	p.Asp119Asp	synonymous	Exon 4 of 20	NP_001122324.1	Q9BXP5-3
	SRRT	NM_001128853.2		c.357C>T	p.Asp119Asp	synonymous	Exon 4 of 20	NP_001122325.1	Q9BXP5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRT	ENST00000611405.5	TSL:1 MANE Select	c.357C>T	p.Asp119Asp	synonymous	Exon 4 of 20	ENSP00000480421.1	Q9BXP5-1
	SRRT	ENST00000614484.4	TSL:1	c.357C>T	p.Asp119Asp	synonymous	Exon 4 of 20	ENSP00000481173.1	Q9BXP5-3
	SRRT	ENST00000618262.4	TSL:1	c.357C>T	p.Asp119Asp	synonymous	Exon 4 of 20	ENSP00000478341.1	Q9BXP5-2

Frequencies

GnomAD3 genomes AF: 0.00241 AC: 367 AN: 152204 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00372

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00286 AC: 702 AN: 245344 AF XY: 0.00280

Gnomad AFR exome AF: 0.000524

Gnomad AMR exome AF: 0.00374

Gnomad ASJ exome AF: 0.00201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00399

Gnomad NFE exome AF: 0.00373

Gnomad OTH exome AF: 0.00732

GnomAD4 exome AF: 0.00340 AC: 4973 AN: 1461274 Hom.: 13 Cov.: 32 AF XY: 0.00331 AC XY: 2406 AN XY: 726958

African (AFR) AF: 0.000597 AC: 20 AN: 33478

American (AMR) AF: 0.00356 AC: 159 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00195 AC: 51 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86244

European-Finnish (FIN) AF: 0.00383 AC: 203 AN: 53064

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00389 AC: 4321 AN: 1111862

Other (OTH) AF: 0.00331 AC: 200 AN: 60378

GnomAD4 genome AF: 0.00240 AC: 366 AN: 152322 Hom.: 1 Cov.: 32 AF XY: 0.00234 AC XY: 174 AN XY: 74464

African (AFR) AF: 0.000505 AC: 21 AN: 41578

American (AMR) AF: 0.00268 AC: 41 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00372 AC: 253 AN: 68026

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.000635 Hom.: 5

Bravo AF: 0.00233

EpiCase AF: 0.00393

EpiControl AF: 0.00379

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.7
DANN	Benign	0.42
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs144415744; hg19: chr7-100479385; COSMIC: COSV61453133; COSMIC: COSV61453133;