chr7-100882125-C-T

Variant names:

• chr7-100882125-C-T
• rs143241109
• NM_015908.6:c.471C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015908.6(SRRT):​c.471C>T​(p.Leu157Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,614,164 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (27 hom.)
• Consequence: SRRT NM_015908.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.231
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-100882125-C-T is Benign according to our data. Variant chr7-100882125-C-T is described in ClinVar as Benign. ClinVar VariationId is 778024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.231 with no splicing effect.
• BS2: High AC in GnomAd4 at 563 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.471C>T	p.Leu157Leu	synonymous	Exon 5 of 20	NP_056992.4
	SRRT	NM_001128852.2		c.471C>T	p.Leu157Leu	synonymous	Exon 5 of 20	NP_001122324.1	Q9BXP5-3
	SRRT	NM_001128853.2		c.471C>T	p.Leu157Leu	synonymous	Exon 5 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.471C>T	p.Leu157Leu	synonymous	Exon 5 of 20	ENSP00000480421.1	Q9BXP5-1
	SRRT	ENST00000614484.4	TSL:1	c.471C>T	p.Leu157Leu	synonymous	Exon 5 of 20	ENSP00000481173.1	Q9BXP5-3
	SRRT	ENST00000618262.4	TSL:1	c.471C>T	p.Leu157Leu	synonymous	Exon 5 of 20	ENSP00000478341.1	Q9BXP5-2

Frequencies

GnomAD3 genomes AF: 0.00370 AC: 563 AN: 152190 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00704

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00371 AC: 934 AN: 251420 AF XY: 0.00366

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.00683

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00513 AC: 7497 AN: 1461856 Hom.: 27 Cov.: 31 AF XY: 0.00491 AC XY: 3570 AN XY: 727230

African (AFR) AF: 0.000478 AC: 16 AN: 33480

American (AMR) AF: 0.00119 AC: 53 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26130

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

South Asian (SAS) AF: 0.000858 AC: 74 AN: 86258

European-Finnish (FIN) AF: 0.00253 AC: 135 AN: 53414

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.00627 AC: 6977 AN: 1111996

Other (OTH) AF: 0.00351 AC: 212 AN: 60396

GnomAD4 genome AF: 0.00370 AC: 563 AN: 152308 Hom.: 2 Cov.: 33 AF XY: 0.00330 AC XY: 246 AN XY: 74476

African (AFR) AF: 0.000698 AC: 29 AN: 41558

American (AMR) AF: 0.00111 AC: 17 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00704 AC: 479 AN: 68016

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00553 Hom.: 0

Bravo AF: 0.00326

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00605

EpiControl AF: 0.00557

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.42
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs143241109; hg19: chr7-100479746; COSMIC: COSV61454473; COSMIC: COSV61454473;