1-145960561-C-G

Variant names:

• chr1-145960561-C-G
• rs782067672
• NM_001039888.4:c.1199G>C

Variant summary

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

The NM_001039888.4(ANKRD34A):​c.1199G>C​(p.Ser400Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/8 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. S400N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ANKRD34A NM_001039888.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

Genes affected

ANKRD34A (HGNC:27639): (ankyrin repeat domain 34A)

ENSG00000280778 (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=0.099867105).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039888.4. 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
	ANKRD34A	NM_001039888.4	MANE Select	c.1199G>C	p.Ser400Thr	missense	Exon 4 of 4	NP_001034977.1	Q69YU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD34A	ENST00000606888.3	TSL:2 MANE Select	c.1199G>C	p.Ser400Thr	missense	Exon 4 of 4	ENSP00000475189.1	Q69YU3
	ENSG00000280778	ENST00000625258.1	TSL:5	c.-29-16523C>G		intron	N/A	ENSP00000487094.1	A0A0D9SG24
	ANKRD34A	ENST00000855736.1		c.1199G>C	p.Ser400Thr	missense	Exon 2 of 2	ENSP00000525795.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432164 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 709426

African (AFR) AF: 0.00 AC: 0 AN: 32818

American (AMR) AF: 0.00 AC: 0 AN: 40910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24568

East Asian (EAS) AF: 0.00 AC: 0 AN: 38520

South Asian (SAS) AF: 0.00 AC: 0 AN: 82124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096848

Other (OTH) AF: 0.00 AC: 0 AN: 59048

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.020	T
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.10	T
PhyloP100		2.8
Sift4G	Benign	1.0	T
Vest4		0.10
gMVP		0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782067672; hg19: chr1-145474527;