19-43612324-C-A

Variant names:

• chr19-43612324-C-A
• rs867398191
• NM_001145641.2:c.203C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145641.2(SRRM5):​c.203C>A​(p.Thr68Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T68I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRRM5 NM_001145641.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12237388).

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.203C>A	p.Thr68Asn	missense	Exon 1 of 1	NP_001139113.1	B3KS81
	ZNF428	NM_182498.4	MANE Select	c.76+1905G>T		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.203C>A	p.Thr68Asn	missense	Exon 1 of 1	ENSP00000414512.1	B3KS81
	ZNF428	ENST00000300811.8	TSL:1 MANE Select	c.76+1905G>T		intron	N/A	ENSP00000300811.2	Q96B54
	SRRM5	ENST00000607544.1	TSL:2	c.203C>A	p.Thr68Asn	missense	Exon 3 of 3	ENSP00000476253.1	B3KS81

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.59
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.096
Sift	Uncertain	0.018	D
Sift4G	Benign	0.43	T
Polyphen		0.96	D
Vest4		0.087
MutPred		0.26		Loss of phosphorylation at T68 (P = 0.0046)
MVP		0.014
MPC		0.055
ClinPred		0.43	T
GERP RS		0.39
PromoterAI		0.0040	Neutral
Varity_R		0.13
gMVP		0.014
Mutation Taster		=99/1	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: rs867398191; hg19: chr19-44116476;