chr2-73214327-G-A

Position:

• chr2-73214327-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006062.3(SMYD5):​c.61G>A​(p.Val21Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMYD5 NM_006062.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

Genes affected

SMYD5 (HGNC:16258): (SMYD family member 5) Predicted to enable histone methyltransferase activity (H4-K20 specific). Involved in negative regulation of transposition and regulation of stem cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0941056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD5	NM_006062.3	c.61G>A	p.Val21Ile	missense_variant	1/13	ENST00000389501.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD5	ENST00000389501.9	c.61G>A	p.Val21Ile	missense_variant	1/13	1	NM_006062.3	P1
SMYD5	ENST00000629411.2	c.61G>A	p.Val21Ile	missense_variant	1/3	5
SMYD5	ENST00000413491.5	c.61G>A	p.Val21Ile	missense_variant, NMD_transcript_variant	1/5	4
SMYD5	ENST00000258100.8	c.61G>A	p.Val21Ile	missense_variant, NMD_transcript_variant	1/8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.12	N;.
REVEL	Benign	0.10
Sift	Benign	0.47	T;.
Sift4G	Benign	0.28	T;T
Polyphen		0.0	B;.
Vest4		0.15
MutPred		0.40		Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);
MVP		0.41
MPC		0.28
ClinPred		0.13	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.028
gMVP		0.22

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: chr2-73441455;