7-100884527-A-C

Variant names:

• chr7-100884527-A-C
• rs780973393
• NM_015908.6:c.917A>C

Variant summary

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

The NM_015908.6(SRRT):​c.917A>C​(p.Asp306Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000293 in 1,432,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: SRRT NM_015908.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06639719).
• BS2: High AC in GnomAdExome4 at 42 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.917A>C	p.Asp306Ala	missense	Exon 7 of 20	NP_056992.4
	SRRT	NM_001128852.2		c.917A>C	p.Asp306Ala	missense	Exon 7 of 20	NP_001122324.1	Q9BXP5-3
	SRRT	NM_001128853.2		c.917A>C	p.Asp306Ala	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.917A>C	p.Asp306Ala	missense	Exon 7 of 20	ENSP00000480421.1	Q9BXP5-1
	SRRT	ENST00000614484.4	TSL:1	c.917A>C	p.Asp306Ala	missense	Exon 7 of 20	ENSP00000481173.1	Q9BXP5-3
	SRRT	ENST00000618262.4	TSL:1	c.917A>C	p.Asp306Ala	missense	Exon 7 of 20	ENSP00000478341.1	Q9BXP5-2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.0000321 AC: 8 AN: 249596 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000293 AC: 42 AN: 1432864 Hom.: 0 Cov.: 44 AF XY: 0.0000337 AC XY: 24 AN XY: 712626

African (AFR) AF: 0.00 AC: 0 AN: 32712

American (AMR) AF: 0.00 AC: 0 AN: 43654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00114 AC: 42 AN: 36818

South Asian (SAS) AF: 0.00 AC: 0 AN: 85940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093754

Other (OTH) AF: 0.00 AC: 0 AN: 58610

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000578 AC: 2 AN: 3476

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	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.0
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.085	T
Polyphen		0.34	B
Vest4		0.32
MutPred		0.23		Gain of MoRF binding (P = 0.0221)
MVP		0.093
ClinPred		0.075	T
GERP RS		3.9
PromoterAI		0.0023	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.2
Varity_R		0.068
gMVP		0.30
Mutation Taster		=89/11	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: rs780973393; hg19: chr7-100482148;