NM_198493.3:c.313G>A

Variant names:

• chr1-173659106-C-T
• NM_198493.3:c.313G>A

Variant summary

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

The NM_198493.3(ANKRD45):​c.313G>A​(p.Glu105Lys) 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. 13/21 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: ANKRD45 NM_198493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50
• Publications: 0 publications found

Genes affected

ANKRD45 (HGNC:24786): (ankyrin repeat domain 45)

ENSG00000285777 (HGNC:):

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=0.26343036).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198493.3. 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
	ANKRD45	NM_198493.3	MANE Select	c.313G>A	p.Glu105Lys	missense	Exon 2 of 6	NP_940895.1	Q5TZF3-2
	ANKRD45	NR_158771.1		n.363G>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD45	ENST00000333279.3	TSL:1 MANE Select	c.313G>A	p.Glu105Lys	missense	Exon 2 of 6	ENSP00000331268.2	Q5TZF3-2
	ANKRD45	ENST00000367712.2	TSL:1	n.344G>A		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000285777	ENST00000648193.1		n.313G>A		non_coding_transcript_exon	Exon 2 of 8	ENSP00000498204.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.14
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Pathogenic	1.0
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.42	T
Sift4G	Uncertain	0.030	D
Vest4		0.42
MVP		0.74
MPC		0.39
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.69
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-173628245; COSMIC: COSV104657949;