7-100884146-A-T

Variant names:

• chr7-100884146-A-T
• NM_015908.6:c.664A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015908.6(SRRT):​c.664A>T​(p.Arg222Trp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRRT NM_015908.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30434906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRRT	NM_015908.6	c.664A>T	p.Arg222Trp	missense_variant	Exon 6 of 20	ENST00000611405.5	NP_056992.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRRT	ENST00000611405.5	c.664A>T	p.Arg222Trp	missense_variant	Exon 6 of 20	1	NM_015908.6	ENSP00000480421.1
SRRT	ENST00000614484.4	c.664A>T	p.Arg222Trp	missense_variant	Exon 6 of 20	1		ENSP00000481173.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.664A>T (p.R222W) alteration is located in exon 6 (coding exon 5) of the SRRT gene. This alteration results from a A to T substitution at nucleotide position 664, causing the arginine (R) at amino acid position 222 to be replaced by a tryptophan (W). 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	0.18
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	.;.;.;D
Eigen	Benign	-0.084
Eigen_PC	Benign	-0.082
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Pathogenic	0.97	D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;L;L
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.96	D;D;D;D
Vest4		0.54
MutPred		0.49		Loss of MoRF binding (P = 0.0469);Loss of MoRF binding (P = 0.0469);Loss of MoRF binding (P = 0.0469);Loss of MoRF binding (P = 0.0469);
MVP		0.11
ClinPred		0.72	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.29

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: chr7-100481767;