chr19-43612353-C-T

Variant names:

• chr19-43612353-C-T
• NM_001145641.2:c.232C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145641.2(SRRM5):​c.232C>T​(p.Pro78Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRRM5 NM_001145641.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.939
• Publications: 0 publications found

Genes affected

SRRM5 (HGNC:37248): (serine/arginine repetitive matrix 5)

ZNF428 (HGNC:20804): (zinc finger protein 428) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058202654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145641.2. 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
	SRRM5	NM_001145641.2	MANE Select	c.232C>T	p.Pro78Ser	missense	Exon 1 of 1	NP_001139113.1	B3KS81
	ZNF428	NM_182498.4	MANE Select	c.76+1876G>A		intron	N/A	NP_872304.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM5	ENST00000417606.3	TSL:6 MANE Select	c.232C>T	p.Pro78Ser	missense	Exon 1 of 1	ENSP00000414512.1	B3KS81
	ZNF428	ENST00000300811.8	TSL:1 MANE Select	c.76+1876G>A		intron	N/A	ENSP00000300811.2	Q96B54
	SRRM5	ENST00000607544.1	TSL:2	c.232C>T	p.Pro78Ser	missense	Exon 3 of 3	ENSP00000476253.1	B3KS81

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.13
DANN	Benign	0.56
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.94
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.0040
Sift	Benign	0.24	T
Sift4G	Benign	0.88	T
Polyphen		0.0070	B
Vest4		0.096
MutPred		0.28		Gain of phosphorylation at P78 (P = 2e-04)
MVP		0.014
MPC		0.015
ClinPred		0.15	T
GERP RS		-5.7
PromoterAI		0.0027	Neutral
Varity_R		0.022
gMVP		0.030
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

hg19: chr19-44116505;