5-56111700-A-G

Position:

• chr5-56111700-A-G

Variant summary

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

The NM_024669.3(ANKRD55):​c.1048T>C​(p.Phe350Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD55 NM_024669.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.21

Genes affected

ANKRD55 (HGNC:25681): (ankyrin repeat domain 55)

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=0.20357215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD55	NM_024669.3	c.1048T>C	p.Phe350Leu	missense_variant	10/12	ENST00000341048.9
ANKRD55	XM_047417710.1	c.562T>C	p.Phe188Leu	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD55	ENST00000341048.9	c.1048T>C	p.Phe350Leu	missense_variant	10/12	2	NM_024669.3	P1
ANKRD55	ENST00000434982.2	c.184T>C	p.Phe62Leu	missense_variant	2/4	1
ANKRD55	ENST00000504958.6	c.919T>C	p.Phe307Leu	missense_variant	8/10	5
ANKRD55	ENST00000505970.2	n.731T>C		non_coding_transcript_exon_variant	7/7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.1048T>C (p.F350L) alteration is located in exon 10 (coding exon 9) of the ANKRD55 gene. This alteration results from a T to C substitution at nucleotide position 1048, causing the phenylalanine (F) at amino acid position 350 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0061	T;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;.
MutationTaster	Benign	0.92	D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.63	N;N;D
REVEL	Benign	0.049
Sift	Benign	0.095	T;T;D
Sift4G	Benign	0.074	T;T;D
Vest4		0.37
MVP		0.48
MPC		0.26
ClinPred		0.87	D
GERP RS		4.3
Varity_R		0.11
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs1303936481; hg19: chr5-55407527;