NM_013241.3:c.642+79A>G

Variant names:

• chr16-67237955-T-C
• rs3852700
• NM_013241.3:c.642+79A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013241.3(FHOD1):​c.642+79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,495,948 control chromosomes in the GnomAD database, including 20,899 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (8942 hom., cov: 33)
  • Exomes 𝑓: 0.093 (11957 hom.)
• Consequence: FHOD1 NM_013241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262
• Publications: 14 publications found

Genes affected

FHOD1 (HGNC:17905): (formin homology 2 domain containing 1) This gene encodes a protein which is a member of the formin/diaphanous family of proteins. The gene is ubiquitously expressed but is found in abundance in the spleen. The encoded protein has sequence homology to diaphanous and formin proteins within the Formin Homology (FH)1 and FH2 domains. It also contains a coiled-coil domain, a collagen-like domain, two nuclear localization signals, and several potential PKC and PKA phosphorylation sites. It is a predominantly cytoplasmic protein and is expressed in a variety of human cell lines. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

SLC9A5 (HGNC:11078): (solute carrier family 9 member A5) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013241.3. 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
	FHOD1	NM_013241.3	MANE Select	c.642+79A>G		intron	N/A	NP_037373.2	Q9Y613
	FHOD1	NM_001318202.2		c.642+79A>G		intron	N/A	NP_001305131.1	A0A068F7M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHOD1	ENST00000258201.9	TSL:1 MANE Select	c.642+79A>G		intron	N/A	ENSP00000258201.4	Q9Y613
	SLC9A5	ENST00000564704.5	TSL:1	n.273T>C		non_coding_transcript_exon	Exon 1 of 16
	FHOD1	ENST00000932114.1		c.924+79A>G		intron	N/A	ENSP00000602173.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35750 AN: 152066 Hom.: 8906 Cov.: 33

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.0931 AC: 125158 AN: 1343764 Hom.: 11957 Cov.: 21 AF XY: 0.0933 AC XY: 62682 AN XY: 671554

African (AFR) AF: 0.656 AC: 20321 AN: 30958

American (AMR) AF: 0.0956 AC: 4153 AN: 43446

Ashkenazi Jewish (ASJ) AF: 0.0394 AC: 961 AN: 24360

East Asian (EAS) AF: 0.0187 AC: 731 AN: 39056

South Asian (SAS) AF: 0.170 AC: 13933 AN: 81860

European-Finnish (FIN) AF: 0.112 AC: 5919 AN: 52688

Middle Eastern (MID) AF: 0.0912 AC: 390 AN: 4276

European-Non Finnish (NFE) AF: 0.0718 AC: 72607 AN: 1011098

Other (OTH) AF: 0.110 AC: 6143 AN: 56022

GnomAD4 genome AF: 0.236 AC: 35846 AN: 152184 Hom.: 8942 Cov.: 33 AF XY: 0.233 AC XY: 17356 AN XY: 74410

African (AFR) AF: 0.634 AC: 26313 AN: 41482

American (AMR) AF: 0.122 AC: 1870 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3472

East Asian (EAS) AF: 0.0211 AC: 109 AN: 5178

South Asian (SAS) AF: 0.166 AC: 800 AN: 4824

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10600

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0711 AC: 4836 AN: 68012

Other (OTH) AF: 0.173 AC: 365 AN: 2108

Alfa AF: 0.119 Hom.: 1369

Bravo AF: 0.250

Asia WGS AF: 0.148 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs3852700; hg19: chr16-67271858;