rs1789885666

Variant names:

• chr7-100884457-C-T
• rs1789885666
• NM_015908.6:c.847C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015908.6(SRRT):​c.847C>T​(p.Pro283Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SRRT NM_015908.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.654
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04244876).
• BS2: High AC in GnomAdExome4 at 7 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.847C>T	p.Pro283Ser	missense	Exon 7 of 20	NP_056992.4
	SRRT	NM_001128852.2		c.847C>T	p.Pro283Ser	missense	Exon 7 of 20	NP_001122324.1	Q9BXP5-3
	SRRT	NM_001128853.2		c.847C>T	p.Pro283Ser	missense	Exon 7 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.847C>T	p.Pro283Ser	missense	Exon 7 of 20	ENSP00000480421.1	Q9BXP5-1
	SRRT	ENST00000614484.4	TSL:1	c.847C>T	p.Pro283Ser	missense	Exon 7 of 20	ENSP00000481173.1	Q9BXP5-3
	SRRT	ENST00000618262.4	TSL:1	c.847C>T	p.Pro283Ser	missense	Exon 7 of 20	ENSP00000478341.1	Q9BXP5-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151892 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461724 Hom.: 0 Cov.: 44 AF XY: 0.00000688 AC XY: 5 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151892 Hom.: 0 Cov.: 28 AF XY: 0.0000135 AC XY: 1 AN XY: 74180

African (AFR) AF: 0.00 AC: 0 AN: 41322

American (AMR) AF: 0.0000656 AC: 1 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2084

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.89
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.65
PrimateAI	Uncertain	0.49	T
Sift4G	Benign	0.33	T
Polyphen		0.0070	B
Vest4		0.17
MutPred		0.22		Gain of phosphorylation at P283 (P = 0.0022)
MVP		0.043
ClinPred		0.056	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.021
gMVP		0.15
Mutation Taster		=97/3	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: rs1789885666; hg19: chr7-100482078;