2-97113864-A-T

Variant names:

• chr2-97113864-A-T
• rs550176856
• NM_001354587.1:c.125A>T

Variant summary

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

The NM_001354587.1(ANKRD36):​c.125A>T​(p.His42Leu) 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. 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. H42R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD36 NM_001354587.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 5 publications found

Genes affected

ANKRD36 (HGNC:24079): (ankyrin repeat domain 36)

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=0.059060305).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354587.1. 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
	ANKRD36	NM_001354587.1	MANE Select	c.125A>T	p.His42Leu	missense	Exon 1 of 76	NP_001341516.1	A6QL64-1
	ANKRD36	NM_198555.4		c.125A>T	p.His42Leu	missense	Exon 1 of 3	NP_940957.3	A6QL64-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD36	ENST00000420699.9	TSL:5 MANE Select	c.125A>T	p.His42Leu	missense	Exon 1 of 76	ENSP00000391950.4	A6QL64-1
	ANKRD36	ENST00000452478.2	TSL:1	n.313A>T		non_coding_transcript_exon	Exon 1 of 3
	ANKRD36	ENST00000461153.7	TSL:5	c.125A>T	p.His42Leu	missense	Exon 1 of 75	ENSP00000419530.3	A6QL64-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.12
DANN	Benign	0.26
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.068	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.33	N
PhyloP100		-1.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.027
Sift	Benign	0.63	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.47		Loss of MoRF binding (P = 0.0793)
MVP		0.35
ClinPred		0.035	T
GERP RS		-1.9
PromoterAI		-0.057	Neutral
Varity_R		0.033
Mutation Taster		=100/0	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: rs550176856; hg19: chr2-97779601;